Chromatography is one of the most important working horses in the purification of biotechnological products. This can be based on ion exchange chromatography, affinity chromatography, size exclusion (or gel filtration) chromatography, hydrophobic interaction chromatography or reversed phase chromatography among others.
Traditionally, chromatographic purifications are carried out in batch mode. This involves one single column that is subsequently loaded, washed, eluted, etc. For treating large volumes or purifying large amounts of product, either very large columns are needed or repeated injections are required. This yields a relatively inefficient mode of operation with a low specific productivity. Such chromatography processes require large amounts of Adsorbent and large amounts of buffers.
Continuous processes are known to have a higher specific productivity and—if carried out in a countercurrent mode—consume much lower amounts of buffer. Continuous countercurrent chromatography processes are generally based on multiple columns. This includes the traditional merry-go-round system, carrousel type systems and static type SMB systems.
Such SMB (Simulated Moving Bed) systems generally use a series of columns with periodically moving inlet and outlet ports. These techniques have been successfully used in the production of petrochemicals and sugars. However, biopharmaceutical production is still based on batch processes. Nonetheless, also batch processes can involve steps that are essentially carried out in a continuous mode. For instance, centrifugation is often performed as a continuous process. In some processes even continuous perfusion systems for the cell culture or fermentation process are being used.
In order to avoid the cleaning of equipment, biopharmaceutical production processes nowadays use wetted components that are for single-use or that are dedicated to one process step of one single product. This cuts down the requirement for cleaning dramatically. In case of single-use wetted components, cleaning can be even completely avoided. The use of single-use bags for storing buffers and intermediate products instead of containers is one very successful example of single-use components in biopharmaceutical industries. In processing relatively small batches, it is also common to use disposable bioreactors, disposable membrane cartridges and tubing.
Existing multicolumn chromatography systems involve complex valve arrangements in order to ensure proper distribution of all flows to all columns. For biotechnology this is undesirable because of the cleaning issues involved. The cleaning of a system in biopharmaceutical production processes should be designed such that it ensures removal of all contaminating compounds from all potentially wetted surfaces. In this respect, equipment with complex internal geometries is very difficult to clean.
Chin and Wang, in “Simulated Moving Bed Equipment Designs”, Separation And Purification Reviews, Vol 33. No 2, pp 77-155, (2004) give some requirements for a truly versatile SMB system, which includes the possibility of performing zone bypasses and allowing configurations in which the number of zones ranges from three to nine or more, allowing easy changes in the configuration.
In one aspect of the invention, it is desirable to provide a valve device that is flexible in the number of connections that can be made and the number of columns that can be added. In another aspect of the invention it is desirable to provide a valve device that limits contamination by using a specific structure. In case only one column is connected to the system, the system would also be suitable for traditional single-column chromatography processes.